Demyelination secondary

We do not discuss the axonal forms of CMT, although they may involve secondary demyelination. Axonal loss is also observed in the demyelinating type 1 CMT (Bjartmar et al 1999). There are some rare autosomal recessive forms called CMT4 which are also demyelinating. 

Secondary demyelination is the loss of myelin secondary to loss of axons. Axonal trophic factors sustain myelin. When the axon is severed or not sustained by its neuron of origin, the axon and then its myelin degenerates. This can happen secondary to infarcts, trauma, toxic, metabolic, or degenerative nervous system diseases. In contrast to primary demyelination, straight and long NF-positive axons are not seen in secondary demyelination. Acutely, the axons crumble into short pieces, and in a few days they are eaten by macrophages and disappear. NF stains thus distinguish secondary from primary demyelination. 

O MS symptoms are a function of the position of lesions within the CNS. Because myelin increases the speed of nerve impulse transmission, demyelination slows the speed of transmission. No impulses can be transmitted if the axon is transected. The primary symptoms of MS are caused by this delay or cessation of impulses. Secondary symptoms of MS result from the primary symptoms. 

Progressive multifocal leukoencephalopathy (PML) is historically a rare demyelinating disease that is usually associated with disorders of the reticuloendothelial system, neoplasias and immunosuppressive therapy [1, 2]. However, it has become more important in clinical medicine because it is frequently seen as an opportunistic secondary infection in immunocompromised persons with AIDS. PML is characterized by focal lesions that are noninflammatory and caused by infection of oligodendrocytes with the JC papovavirus. 

Like spinal cord trauma, traumatic head injury consists of a primary injury, attributable to the mechanical insult itself, and a secondary injury, attributable to the series of systemic and local neurochemical changes that occur in brain after the initial traumatic insult (Klussmann and Martin-Villalba, 2005). The primary injury causes a rapid deformation of brain tissues, leading to rupture of neural cell membranes, release of intracellular contents, and disruption of blood flow and breakdown of the blood-brain barrier. In contrast, secondary injury to the brain tissue includes many neurochemical alterations such as release of cytokines, glial cell reactions involving both activated microglia and astroglia, and demyelination... 

MS is an autoimmune disease that attacks the myelin sheath of oligodendrocytes around the neuronal axons. This allows the axonal cytoskeleton to be damaged, bringing about secondary axonal loss and persisting neurological dysfunction. The characteristic pathology is of a lesion or plaque in the CNS white matter, formed by inflammation and demyelination and these can be classified into active, chronic active, or chronic silent plaques [86]. 

Diphtheria toxin, inorganic lead, and tellurium are considered toxicants that cause demyelination through injury to the myelinating cell. The mechanism of action of diphtheria toxin was discussed in Section 30.1. The mechanism by which inorganic lead causes Schwann cell injury and demyelination is not well understood, but may be related to uncoupling or inhibition of oxidative phosphorylation secondary to interference of lead with some aspect of ion transport across the mitochondrial membrane. 

An inconvenient but more descriptive name for this MS is intermittent, patchy demyelination. This clumsy term makes clear that multiple sclerosis is unlikely to be a single entity in terms of cause (etiology) or disease mechanisms (pathophysiology). In principle, any conditions or combination of conditions that lead to intermittent, patchy demyelination are forms of multiple sclerosis. If a clear cause can be identified, the condition is by convention not referred to as multiple sclerosis. The disease is therefore by definition of unclear etiology. The neurology literature of the last 100 years contains confident declarations that multiple sclerosis has been proven to be a viral disease, that it has been proven not to be a viral disease, that it has been proven to be an immune disease, that immune mechanisms in multiple sclerosis have been shown to be secondary to the disease process, and so on. 

Axonal damage secondary to myelin loss is a major cause of sensory, motor, and cognitive disabilities in adult MS (Bjartmar and Trapp, 2001). The lack of myelin recovery may be due primarily to deficiency in the genesis of OPCs and in their maturation in the adult CNS (Franklin, 2002 Stangel and Hartung, 2002). Limited myelin regeneration is observed in early demyelinating lesions in MS (Wolswijk,... 

Figure 20.1. Hypotlietical scheme of tlie immune response in acute inflammatory demyelinadng polyiadiculoneuiopatliy (AIDP) Inflammatory cells migrate from die systemic immune compartment dnough die damaged blood-nei ve banier into die endoneuiium. Inflammatory infiltrates, which contain T-lymphocytes and macrophages cause marked segmental demyelination and secondary axonal degeneradon (B B-cell T T-cell M0 Macrophage).

Preparations for intravenous administration are mainly used in patients with general immune deficiency states (primary or secondary) or diseases like idiopathic thrombo-cjhopenic purpura (ITP) and autoimmune diseases (5,6). Neurological disorders (for example Guillain-Barre syndrome and chronic demyelinating polyneuropathy) have been treated with intravenous immunoglobulin (7-9). 

The pathology of the infection is due to inflammatory changes associated with an induced autoimmune demyelination of nerve cells. Interestingly, the immunosuppressive action of components of the parasite s membrane are probably responsible for frequent secondary infections such as pneumonia. Liberation of common surface antigens (the mechanism involved in immune evasion) in every trypanolytic crisis (episode of trypanosome lysis) leads to antibody and cell-mediated hypersensitivity reactions. It is believed that some cytotoxic and pathological processes are the result of biochemical and immune mechanisms. 

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